Abstract

BACKGROUND/OBJECTIVE:

In addition to cirrhosis of the liver, Wilson's disease leads to copper accumulation and widespread degeneration of the nervous system. Delayed visual evoked potentials (VEPs) suggest changes to the visual system and potential structural changes of the retina.

METHODS:

We used the latest generation of spectral domain optical coherence tomography to assess the retinal morphology of 42 patients with Wilson's disease and 76 age- and sex-matched controls. We measured peripapillary retinal nerve fiber layer (RNFL) thickness and total macular thickness and manually segmented all retinal layers in foveal scans of 42 patients with Wilson's disease and 76 age- and sex-matched controls. The results were compared with VEPs and clinical parameters.

RESULTS:

The mean thickness of the RNFL, paramacular region, retinal ganglion cell/inner plexiform layer and inner nuclear layer was reduced in Wilson's disease. VEPs were altered with delayed N75 and P100 latencies, but the N140 latency and amplitude was unchanged. An analysis of the laboratory parameters indicated that the serum concentrations of copper and caeruloplasmin positively correlated with the thickness of the outer plexiform layer and with N75 and P100 VEP latencies.

CONCLUSION:

Neuronal degeneration in Wilson's disease involves the retina and changes can be quantified by optical coherence tomography. While the VEPs and the thickness of the outer plexiform layer appear to reflect the current copper metabolism, the thicknesses of the RNFL, ganglion cell/inner plexiform layer, inner nuclear layer and the total paramacular thickness may be the best indicators of chronic neuronal degeneration.

The areas of measurement are marked in an image of the fundus. The RNFL was measured in a circular scan centered on the optic disc and the macular thickness in scans around the fovea. The manual segmentation of the retinal layers was performed in a horizontal scan through the center of the fovea. The scatter plots display the thickness of the RNFL (B) and the total macular thickness (C). Each point represents the mean of the two eyes of one patient. The mean of all patients is indicated by a horizontal bar. Significant differences are indicated by asterisks (p<0.05, two-tailed t-test).

Manual segmentation: the thickness of GCIP and INL is reduced in Wilson’s disease. A

The different retinal layers were manually segmented in single horizontal foveal scans and the images are displayed as negatives to better differentiate the different layers. The thickness of the different layers was measured at the vertical lines indicating the thickest point, both nasally and temporally of the fovea, except for the ONL, which was measured centrally along the vertical line. B–E Scatter plots of the mean thickness of the different retinal layers. Each point represents the mean of the two eyes of one patient. The mean of all patients is indicated by a horizontal bar. Significant differences are indicated by asterisks (p<0.05, two-tailed t test); non-significant differences are indicated as n.s.

Visual evoked potentials: N75 and P100 latencies are prolonged in Wilson’s disease. A

Representative VEP curves of Wilson’s disease patients and controls are displayed. B–E Scatter plots of the mean VEP parameters. Each point represents the mean of the two eyes of one patient. The mean of all patients is indicated by a horizontal bar. Significant differences are indicated by asterisks (p<0.05, two-tailed t test); non-significant differences are indicated as n.s.

The significant correlations between the thickness of the different retinal layers and the VEP parameters of the patients’ left eyes are displayed and the Pearson r is indicated (p<0.05, Pearson). H The continuous lines resemble the linear regression including, and the dotted lines excluding, an outlier with beginning hepatic failure (the outlier is marked as unfilled dot, Pearson r is indicated considering the outlier).

The significant correlations between the laboratory parameters and the mean thickness of the retinal layers and VEP parameters of both eyes are shown and the Pearson or Spearman r is indicated (p<0.05 including the outlier, all comparisons were made using a Pearson analysis except for the Wilson Score, which was analyzed using a Spearman analysis). A–D The continuous lines resemble linear regressions including, and the dotted lines excluding, an outlier with beginning hepatic failure (the outlier is marked as unfilled dot, Pearson r is indicated considering the outlier).